Cationic currents induced by Clostridium perfringens type A enterotoxin inhuman intestinal CaCO-2 cells

Clostridium perfringens type A produces an enterotoxin that induces diarrho ea experimentally in man and animals. The enterotoxin causes increased memb rane permeability in susceptible cells which is thought to be due to pore f ormation in the host cell membrane. The effect of purified C, perfringens e nterotoxin on intact intestinal CaCO-2 monolayers was examined in Ussing ch ambers and on single cells by whole-cell patch clamp. Mucosal application o f C. perfringens enterotoxin resulted in prompt increases in short-circuit current coupled with a reduction in transepithelial resistance consistent w ith movement of sodium and other cations smaller than diethanolamine from m ucosa to serosa. These changes were independent of extracellular calcium. I ncreases in short-circuit current were also observed in the apical membrane s of CaCO-2 monolayers permeabilised across the basolateral membrane with n ystatin, Currents were blocked by subsequent exposure to mucosal barium and zinc. Zinc also prevented the development of the current increases in apic al membranes. Cationic currents were also observed following exposure of si ngle CaCO-2 cells in whole-cell patch clamp recordings. These data indicate that C, perfringens enterotoxin is able to form cation permeant pores in t he apical membrane of human intestinal CaCO-2 epithelia and the increases i n short-circuit current can be prevented by pre-exposure to zinc ions.